The American Society of Breast Surgeons position statement on BRCA genetic testing suggests that any of the following features should prompt education and referral to genetic counseling [32]:

Statistical models intended to provide a likelihood of having an underlying BRCA1 or BRCA2 mutation have been developed and incorporate the personal and family history variables described above. Available models include BRCAPRO and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm [33, 34].

A detailed and comprehensive family history should be obtained by the clinician considering genetic testing for any patient. In regard to testing for BRCA1 and BRCA2 breast cancer syndromes, it must be recognized that these genes carry not only increased risk for breast cancer, but for other cancers as well. As such, a three-generation family history is recommended, which should elicit details about any cancers diagnosed in relatives, with particular attention to cancers of the breast, ovaries, endometrium, thyroid, adrenal, pancreas, brain, or soft tissues. Furthermore, as BRCA1 and BRCA2 are autosomal dominant and may be inherited from either parent, both maternal and paternal family histories should be thoroughly obtained. When possible, other important details to collect in the family history include age at diagnosis of cancer, risk reduction variables including chemoprevention or prophylactic operations, exposure to carcinogens, hormone and reproductive history, and previous breast biopsies. As these details are sophisticated, verification from medical records is recommended, whenever possible [35].

There are several factors that may render the family history less informative. A small family size, or a low number of the susceptible gender for gender-specific cancers, may decrease sensitivity to detect genetic predisposition syndromes. Furthermore, prophylactic operations that remove the susceptible organs create uncertainty as to whether cancer would have developed in that family member. Deaths at an early age, before the age of onset of inherited cancer syndromes, may limit the utility of the family history. If any of these factors is present, the probability of BRCA1 or BRCA2 mutation may be underestimated [36].

When the decision has been made to pursue genetic testing based on the available personal and family history, the recommended strategy is to test a family member who has already been diagnosed with cancer. This recommendation follows from the fact that a negative test in an unaffected person is rather inconclusive. It would remain unknown whether a gene mutation exists in the family, as the tested unaffected person may simply have not inherited the gene that is indeed present in other family members. Additionally, those who undergo full BRCA1 and BRCA2 gene sequencing may have a result indicating a variant of unknown significance, which indicates a DNA mutation that may or may not confer increased cancer risk.

Furthermore, if an already diagnosed person is tested, and a mutation is revealed, it allows subsequent family members to be tested only for the specific gene mutation already identified as the culprit within the family; therefore, it saves additional family members from full genetic sequencing of BRCA1 and BRCA2. In high-risk ethnic populations, such as Ashkenazi Jewish, Icelandic, and Finnish, who in general harbor increased frequency of specific founder mutations, an accepted strategy is to first test the individual specifically for the founder mutation. If the initial test is negative, proceeding to full sequencing of the BRCA1 and BRCA2 genes is then recommended.

There are several possible outcomes of genetic testing for BRCA1 or BRCA2 mutations. First, a test may indicate the existence of a known mutation causing abnormal function of the BRCA1 or BRCA2 protein. This result indicates an increased risk of breast, ovarian, and other cancers, as discussed previously. Patients with this result should then be managed according to guidelines for those with increased risk, which will include surveillance, chemoprevention, or prophylactic operations. A negative result, indicating no identified mutation of BRCA1 or BRCA2, must be interpreted in the context of personal and family history. In a patient with a known gene mutation in the family, a negative result for that specific mutation will mean that the patient has not inherited the trait; his or her risk for cancer is then considered to be equivalent to the general population and is based on factors recognized to be associated with cancers in established risk estimation models. In a patient already diagnosed with cancer, a negative result may have one of several interpretations. It may indicate that a gene mutation is not present within the family, or that a mutation does exist, but cannot be identified with current sequencing technology. It is also possible that a BRCA mutation may exist within a family, while a tested individual with cancer has a sporadic form of cancer. Finally, genetic testing for BRCA gene mutations may have an indeterminate result. That is, there may be small mutations, located in non-critical gene domains, that have unknown consequences for the functional protein. This result confers an unknown cancer risk.

In those already diagnosed with cancer and suspected of having a genetic predisposition syndrome, testing should be considered before definitive treatment plans have been decided, according to the patient’s preferences. The result of the genetic test may inform the decisions regarding treatment options. For example, a woman may use the information to decide whether to pursue breast conservation or mastectomy on the affected side and may additionally consider contralateral prophylactic mastectomy based on the results of the genetic testing. However, some patients may elect to proceed with treatment for the primary cancer without genetic testing results.

The implication of genetic testing for hereditary cancer on health insurance coverage has been a concern of patients and may contribute to anxiety surrounding the test. In general, genetic test results are protected from disclosure to health insurance providers. It is illegal in the United States to deny insurance coverage based on genetic testing results and similarly illegal to consider genetic information as a preexisting condition, owing to protections set forth in the Health Insurance Portability and Accountability Act (HIPAA) of 1996. Furthermore, the federal Genetic Information Nondiscrimination Act (GINA) of 2008 prohibits discrimination based on genetic test results. Patients can generally be reassured that there is little risk to future health insurance coverage based on genetic testing results alone; however, insurance providers may inquire about cancer diagnoses within the family and the individual.

For many years, a company known as Myriad Genetics held patents making it the exclusive provider of BRCA1 and BRCA2 genetic testing in the United States. The tests were costly, at up to $4,000, which may have restricted access for some patients. In 2013, the Supreme Court issued a ruling in Association for Molecular Pathology v. Myriad Genetics, Inc., which changed the landscape of genetic testing, not only for BRCA1 and BRCA2 but with broad implications for cancer diagnostics in general. In essence, the court justices determined that human genes are not eligible for patents. Their decision was based upon the premise that DNA sequences are naturally occurring, and merely sequencing a naturally occurring phenomenon is not adequately inventive to deserve a patent. Consequently, the patent held by Myriad, which provides a result by comparing an individual’s isolated BRCA1 and BRCA2 sequences to reference sequences, was invalidated. Since that decision, a number of competitors have entered the market and will offer BRCA1 and BRCA2 diagnostic genetic testing. This competition in the market will lead to lower prices for these tests and may improve access for certain patients [37, 38].